Examining c-di-GMP and possible quorum sensing regulation in Pseudomonas fluorescens SBW25:links between intra and inter-cellular regulation benefits community cooperative activities such as biofilm formation

Bacterial success in colonizing complex environments requires individual response to micro-scale conditions as well as community-level cooperation to produce large-scale structures such as biofilms. Connecting individual and community responses could be achieved by linking the intracellular sensory and regulatory systems mediated by bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) and other compounds of individuals with intercellular quorum sensing (QS) regulation controlling populations. There is growing evidence to suggest that biofilm formation by many pseudomonads is regulated by both intra and intercellular systems, though in the case of the model Pseudomonas fluorescens SBW25 Wrinkly Spreader in which mutations increasing c-di-GMP levels result in the production of a robust cellulose-based air-liquid interface biofilm, no evidence for the involvement of QS regulation has been reported. However, our recent review of the P. fluorescens SBW25 genome has identified a potential QS regulatory pathway and other QS–associated genes linked to c-di-GMP homeostasis, and QS signal molecules have also been identified in culture supernatants. These findings suggest a possible link between c-di-GMP and QS regulation in P. fluorescens SBW25 which might allow a more sophisticated and responsive control of cellulose production and biofilm formation when colonising the soil and plant-associated environments P. fluorescens SBW25 normally inhabits.Анализ ц-ди-ГМФ и возможного чувства кворума у Pseudomonas fluorescens SBW 25: связь между внутри и межклеточной регуляцией способствует кооперативному поведению в сообществе и формированию биоплёнкиУспешность бактериальной колонизации сложных экониш требует индивидуального ответа на изменения условий на микроуровне равно как и кооперации на уровне сообщества для продукции таких крупно масштабных структур как биоплёнки. Координация индивидуальных ответ ов и ответов сообщества может быть достигнута путем связывания внутриклеточных сенсорных и регуляторных систем, опосредуемых бис-(3',5')-циклическим димерным гуанозинмонофосфатом (ц-ди-ГМФ) и другими соединениями индивидуумов с межклеточной регуляцией - чувством кворума (ЧК), контролирующем популяци ю. Накапливается всё больше доказательств того, что формирование биопленки многими псевдомонадами регулируется как внутри клеточными, так и меж клеточными регуляторными системами, хотя в случае модельной Pseudomonas fluorescens SBW25 Wrinkly Spreader, у которой мутации, повышающ ие уровни ц-ди-ГМФ, приводят к созданию прочной целлюлозной биоплёнки на границе раздела фаз воздух-жидкость, не было обнаружено ни ка кого свидетельства вовлечения кворум-зависимой регуляции. Однако наш недавний обзор генома P. fluorescens SBW25 выявил потенциальный ЧК-зависимый регуляторный пу ть и другие ЧК-зависимые гены, связанные с гомеостазом ц-ди-ГМФ, а молекулы ЧК-сигналинга были идентифицированы в культуре. Эти данные свидетельствуют о возможной связи между ц-ди-ГМФ-регуляцией и ЧК у P. fluorescens SBW25, что позволяет более сложный и гибкий контроль над продукцией целлюлозы и образовани ем биопленки при колонизации почв и экониш, aссоциированных с растениям и, - естественными средами обитания P. fluorescens SBW25

Lipid profile indices in young people with different types of diabetes mellitus

Of all types of diabetes mellitus (DM), type 1 diabetes mellitus (DM1) and type 2 diabetes (DM2) are most often diagnosed in young people. However, up to 10 % of all cases of DM diagnosed at a young age are monogenic forms of DM – MODY (Maturity-Onset Diabetes of the Young), the most common forms of which are MODY2 (GCK-MODY) and MODY3 (HNF1AMODY). These genetic forms of DM are poorly understood, so the investigation of their clinical and biochemical parameters, including lipid profile, and comparison with more studied forms of DM is of high importance. The aim of this study was to analyze the characteristics of the lipid profile in patients aged 18–45 years with DM1, DM2, GCK-MODY and HNF1A-MODY. Material and methods. In 56 patients diagnosed by the molecular genetic method MODY, as well as in 82 patients with DM2 and 14 patients with DM1, matched by sex, age, a lipid profile was studied. Results. There were no statistically significant differences in total cholesterol and low-density lipoprotein cholesterol between young patients with different types of DM. In HNF1a-MODY, the highest level of triglycerides was revealed; in DM1, the level of high-density lipoprotein cholesterol was significantly higher than in other types of DM. Among the changes in the lipid profile among all types of DM, hypercholesterolemia was more often determined

GCK-MODY diabetes course in persons over 18 years of age: prospective observation

Most young patients with hyperglycemia have type 1 diabetes and type 2 diabetes but up to 10% of all cases of the disease occur in MODY (Maturity Onset Diabetes of the Young). Published abstracts show features of the debut, laboratory and genetic characteristics of MODY in the Russian population. However there is a small amount of data on the clinical course of this nosology in the Russian Federation.Aim: To investigate the characteristics of the 3-year course of GCK-MODY diagnosed after 18 years.Materials and methods: 85 probands and 46 relatives of the first and second degrees of kinship with a clinical diagnosis of GCK-MODY were examined: biochemical and hormonal blood tests, ultrasound, molecular genetic studies. Patients were invited for a follow-up visit 3 years after verification of the pathogenic mutations associated with GCK-MODY. Examination, biochemical and hormonalanalyzes , ultrasound were done in second visit.Results: The diagnosis GCK-MODY was verified by a molecular genetic study in 25 probands (29.4%). In 33 of 46 (71.7%) relatives of patients with GCK-MODY were diagnosed identical mutations. In 31 patients with GCK-MODY diagnosed after 18 years, a dynamic observation was performed for three years. Most patients over 18 years of age did not have clinical manifestations of carbohydrate metabolism disorders when diagnosing GCK-MODY and follow up visit. Skin rashes and allergic reactions prevailed among concomitant pathologies. Patients with GCK-MODY had preserved β-cell secretion, HbA1c targets were achieved. Low fasting hyperglycemia prevailed which persisted even after treatment correction. Among the characteristics of carbohydrate metabolism, biochemical, lipid and hormonal parameters during GCK-MODY verification and after three years of observation no significant differences were obtained, which indicates a stable course of the disease. Half of the patients achieved normoglycemia by rational nutrition, two people with GCK-MODY within three years after determining the diagnosis were transferred from insulin therapy to oral glucose-lowering drugs. Among oral glucose-lowering drugs prior to GCK-MODY verification most patients used metformin, 3 years later — dipeptidyl peptidase-4 inhibitors.Conclusion. The results of a three-year follow-up of a group of patients with GCK-MODY demonstrate a non-progressive course of this type of diabetes with stable indicators of carbohydrate metabolism and low fasting hyperglycemia that persists after 3 years of observation. With the verification of GCK-MODY and the achievement of the target values of glycated hemoglobin and postprandial glycaemia by rational nutrition, even if a low level of fasting hyperglycemia is determined, the prescription of oral glucose-lowering drugs is not indicated in most cases

Base mucronutrients and food groups consumption, associations with the risk of fatal cardiovascular disease development in people with type 2 diabetes: a prospective cohort study

Aim. To study the relation between the consumption of the main macronutrients and food groups with the risk of fatal outcomes from cardiovascular diseases (CVD) in people with newly diagnosed diabetes and those who are informed about type 2 diabetes mellitus (T2DM). Material and methods. This prospective analysis included 681 people (284 men and 397 women) with T2DM at baseline HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) 2003 (05) – December 31, 2018 and averaged 14.7 ± 0.7 years. There were 207 incident CV mortality during follow-up period (107 men, 100 women). The questionnaire on the presence of T2DM included information on the awareness of individuals about the presence of T2DM (“Did the doctor tell you that you have T2DM?”). The actual nutrition data included information on the consumption of 147 foods. The hazard ratio was estimated using Cox regression. Results and discussion. In men who aware of T2DM, the risk of developing a fatal CV event decreases with an increase in the consumption of “all-season” fruits (HR 0.413; 95 % confidence interval (CI) 0.234-0.786) and increases with an increase in the consumption of chicken eggs (HR 1.907 95 % CI 1.051-3.437), and alcohol (HR 1.031; 95 % CI 1.001- 1.061). In men who are unaware of T2DM, with an increase in nut consumption, the risk of developing fatal CV events decreases (HR 0.821; 95 % CI 0.679-0.992) and increases with increasing consumption of dairy products (HR 1.105; 95 % CI 1.000-1.221). In women aware of T2DM, consumption of white bread increases the risk (HR 1.489; 95 % CI 1.105-2.004), on the contrary, consumption of black bread reduces the risk of an undesirable outcome (HR 0.575; 95 % CI 0.424-0.818). Conclusions. In men who aware of T2DM, the most significant risk factors were the poor all-season fruits intake and excessive chicken eggs consumption. In women with type 2 diabetes, an increase in white bread consumption is of importance to increasing the risk of an undesirable CV outcome, and an increase in black bread consumption counts for reducing the risk

Behavioral and social risk factors for metabolically unhealthy obesity: data form a 12-year prospective study in the Russian population

Aim. To study the contribution of behavioral and social risk factors to the development of metabolically unhealthy obesity (MUO) according to a prospective study in the Russian population.Material and methods. From the HAPPIE project, 3197 people aged 45-69 years with a body mass index ≥30 kg/m2 were selected, who had all the necessary parameters for obesity phenotype determination. The prospective analysis included the first (2003-2005) and third screenings (2015-2017). A subsample was formed (n=1275; 276 men — 22%, 999 women — 78%). The mean follow-up period was 12,4 years. IDF criteria (2005) were taken for analysis.Results. Men with a metabolically healthy obesity (MHO) phenotype most often have a secondary and higher education, while women with MHO — vocational and secondary education. In women, secondary education was most often noted. Among persons with obesity, both men and women are more often not single, while having MUO as follows: 56,8% and 34,2%, respectively. Men and women have a low-intensity activity, regardless of the obesity phenotype. The prevalence of smoking in the present time does not differ in the MHO and MUO groups. Metabolically healthy women consume more alcohol than those with MUO. In men with sedentary lifestyle and fasting hyperglycemia, the risk of MUO over a 12-year follow-up period was significantly higher. In women, the risk of conversion from MHO to MUO is increased when blood pressure (BP) is ≥130/85 mmHg.Conclusion. In the Russian population, the risk of MUO in men increases with a level of physical activity <3 h/week and a blood glucose level ≥6,1 mmol/l; in women, only BP ≥130/85 mm Hg contributes to the development of MUO

Diabetes mellitus associated with the mutation of the ABCC8 gene (MODY 12): features of clinical course and therapy

Maturity-Onset Diabetes of the Young (MODY) is a heterogeneous group of diseases associated with genes mutations leading to dysfunction of pancreatic β-cells. Among the 14 identified MODY variants, MODY 1–5 are the most studied. The article reports a MODY 12 clinical case, with mutation in ABCC8, encoding the sulphonylurea receptor. Diabetes mellitus manifested in a 27-year-old man with hyperglycaemia up to 24 mmol/L, without ketosis. Non-proliferative diabetic retinopathy, microalbuminuria, dyslipidaemia and carotid atherosclerosis were revealed upon initial examination. The levels of pancreatic islet cell antibodies and glutamate decarboxylase antibodies were negative, while the level of C-peptide was within the normal range. Insulin therapy in the basal-bolus regimen was provided with a gradual dose reduction due to frequent hypoglycaemia. The preproliferative retinopathy with macular oedema was revealed after 4 months of therapy, and panretinal photocoagulation of both eyes was performed. A molecular genetics study revealed a mutation in the gene ABCC8, the same mutation was found in patient’s mother and uncle. Insulin therapy was cancelled, and the treatment of gliclazide MR 60 mg/day was initiated, which resulted in extreme glycaemic excursions. Thereby, sodium–glucose cotranporter-2 (SGLT2) inhibitor dapagliflozin 10 mg/day was added. A reduction in glucose variability parameters were observed on combination therapy. After 6 months till 1.5 years of treatment, glycaemic control was optimal, no hypoglycaemic episodes were observed. This case study demonstrates clinical features of MODY 12, and the potential of combination of sulfonylurea and SGLT2 inhibitor in the treatment of this disease

Тhe prevalence of metabolically healthy obesity: data from the epidemiological survey in of Novosibirsk

Background: Obesity is associated with numerous metabolic complications, such as type 2 diabetes mellitus (DM2), dyslipidemia, arterial hypertension (AH), cardiovascular diseases and some forms of cancer. Nevertheless, the literature describes a group of obese individuals who are more resistant to the development of metabolic disorders. At present, this phenomenon is known as "Metabolically healthy obesity", "metabolically healthy obesity" (MZO). Despite the presence of excess weight or obesity, a favorable metabolic profile can be observed in this cohort of patients, characterized by preserved insulin sensitivity, absence of arterial hypertension, normal lipid, hormonal profile, absence of inflammation and unchanged hepatic transaminases. Aims: To study the prevalence of metabolically healthy obesity (MHO) and its characteristics in men and women at the age of 45–69 years in Novosibirsk. Materials and methods: To study covered 3197 persons from the base of the international project HAPPIE. They had a body mass index (BMI ≥ 30 kg/m²). «Metabolically healthy obesity» was determined as obesity (BMI ≥ 30 kg/m², with 2 and fewer components of metabolic syndrome (MS) by criteria NCEP ATP III, 2001. Statistical analisys SPSS-13. Results: The prevalence of metabolic healthy obesity (MHO) was 42% (38% for men and 43% for women). The examined people with MHO have reliably more favorable average level of TG, HDL-cholesterol, indicators of blood glucose, systolic arterial pressure and diastolic arterial pressure and less waist circumference. In the groups withMHO and MS abdominal obesity is common in men at 95 and 71%, in women at 99 and 90%; hyperTG – in men at 74 and 9%, in women at 72 and 5,5%; lower level HDL-cholesterol in 16 and 1% for men, and in 44,5% and 3% for women; AP in 96 and 77% and 94 and 71% in men and women respectively, the frequency fasting of hyperglycaemia 77 and 21% in men and 60 and 5% in women was markedly different. According to the data obtained by us, the frequency in the sample is high and amounted to 42%. In the subgroup the most commonly found is the MHO phenotype – 53%, than in the men -38%, р <0,001 Conclusions: According to our data, the frequency of metabolic healthy obesity in the sample is high and amounted to 42%. In the female subgroup, a metabolically healthy phenotype is more common 43% than in the male 38%, p <0.001. Metabolically healthy obese individuals are characterized by a significantly lower incidence of fasting hyperglycaemia and dyslipidemia